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An Iterative O ‐Methyltransferase Catalyzes 1,11‐Dimethylation of Aspergillus fumigatus Fumaric Acid Amides
Author(s) -
Kalb Daniel,
Heinekamp Thorsten,
Schieferdecker Sebastian,
Nett Markus,
Brakhage Axel A.,
Hoffmeister Dirk
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600293
Subject(s) - aspergillus fumigatus , fumaric acid , chemistry , methyltransferase , amide , biochemistry , methylation , biosynthesis , enzyme , stereochemistry , natural product , methionine , coumarin , tyrosine , amino acid , organic chemistry , gene , biology , microbiology and biotechnology
S ‐adenosyl‐ l ‐methionine (SAM)‐dependent methyltransfer is a common biosynthetic strategy to modify natural products. We investigated the previously uncharacterized Aspergillus fumigatus methyltransferase FtpM, which is encoded next to the bimodular fumaric acid amide synthetase FtpA. Structure elucidation of two new A. fumigatus natural products, the 1,11‐dimethyl esters of fumaryl‐ l ‐tyrosine and fumaryl‐ l ‐phenylalanine, together with ftpM gene disruption suggested that FtpM catalyzes iterative methylation. Final evidence that a single enzyme repeatedly acts on fumaric acid amides came from an in vitro biochemical investigation with recombinantly produced FtpM. Size‐exclusion chromatography indicated that this methyltransferase is active as a dimer. As ftpA and ftpM homologues are found clustered in other fungi, we expect our work will help to identify and annotate natural product biosynthesis genes in various species.